QNAS QNAS QnAs with Fraser Stoddart

Christopher Samoray, Science Writer

The design of tiny machines is not a new idea. In the the ring darts back and forth about 1,000 times a second, 1950s, physicist Richard Feynman predicted the devel- at room temperature, in solution between the two recog- opment of nanotechnology and embodied the idea of nition sites. This moment was a defining one for molecular miniaturization in his 1959 lecture “Plenty of Room at the nanotechnology: that is, the invention of MIMs, wherein Bottom” (1). In recent decades, nanotechnology has come we can witness translational motion between the compo- into its own and propelled the careers of many re- nent parts, namely rings and dumbbells. That was about searchers. Among them is Sir Fraser Stoddart, a National the time that I started to use the term “molecular nano- Academy of Sciences member and chemist at Northwest- technology.” I felt the time was right for chemists to join in ern University. Stoddart’s research focuses on mechanos- the description of these MIMs in that context. tereochemistry, a branch of chemistry that describes the spatial organization of atoms in mechanically bonded PNAS: Along with chemists Jean-Pierre Sauvage and molecules (2). Stoddart’s work has fueled a number of Bernard Feringa, you were awarded the 2016 Nobel nanotechnology advances, including the development Prize in Chemistry. For your part, the selection com- of molecules, called bistable rotaxanes, which can be in- mittee recognized your work on bistable rotaxanes, the corporated into nano-sized machinery. For his contribu- mechanically interlocked molecules that are reminis- tions to the field, Stoddart shared the 2016 Nobel Prize in cent of a dumbbell with a ring attached around the Chemistry. Stoddart spoke to PNAS about winning the center. Can you describe how [a] rotaxane maintains its Nobel Prize and the future of molecular nanotechnology. shape, and the construction process involved in making arotaxanemolecule? PNAS: How did you first become interested in molec- ular nanotechnology? Stoddart: The dumbbell and ring components are held together by a mechanical bond. The point about this Stoddart: I can put a date of 1991 on it. This year is mechanical bond is that it’s a new bond in chemistry. the one in which we published, in the Journal of the It’s not a chemical bond. It doesn’t involve the sharing American Chemical Society, a short communication of electrons, as in a covalent bond or a coordinative bond entitled “A molecular shuttle” (3). It is a mechanically involving a transition metal. It is a physical bond, and to interlocked molecule (MIM) based on a dumbbell with that extent it’s repulsive. Of course, that repulsion is over- two recognition sites on the rod portion for a ring to come by a whole gamut of weak interactions that allow us hover around. Using NMR spectroscopy, we showed that to bring the dumbbell component together with the ring component. We have devised several different ways of making rotaxanes. The dumbbell can be made first of all, and then a ring clipped around it. We call this protocol the clipping approach. The other approach that we use commonly is “threading followed by stoppering.” A rod portion with recognition sites on it traps the ring and then stoppers can be added to each end to form a dumbbell with the ring encircling it, forming a rotax- ane. Put another way, we make a one-to-one complex between the rod and the ring, and then carry out chemical reactions to put the stoppers in place. A third approach that we have developed is called slippage, where—provided we get the internal diameter of the ring just right with respect to the external diameter of the stopper—we can entice the rings to go on to the dumbbells in certain solvents. Also, one ex-member of the group quite ingeniously has come up with the trick of swelling the stoppers; the ring is threaded onto the dumbbell and then some chemistry is done to make Fraser Stoddart. Image courtesy of Jim Prisching (photographer). the stopper larger in diameter. That keeps the ring on

190–191 | PNAS | January 10, 2017 | vol. 114 | no. 2 www.pnas.org/cgi/doi/10.1073/pnas.1619654114 Downloaded by guest on September 26, 2021 forever. Another approach involves the shrinking of be said, however, that motors and machines are much the ring. different from switches.

PNAS: You have incorporated rotaxane into devices, PNAS: Has your life changed after the Nobel Prize? such as a “molecular elevator,” capable of raising itself 0.7 nanometers above a surface; artificial muscles, in Stoddart: I’m still trying to work it out. It’s life chang- which the rotaxane promotes bending in the structure; ing. I’m down to three hours of sleep a day at the and novel computer chips. Can you talk about the po- moment. I’m racing around the world because I’m still tential applications for these rotaxane-based creations? trying to maintain some sort of program going that was in place before the announcement. It’s pretty Stoddart: I think the emphasis is on potential. MIMs, overwhelming. I’ve not really been trained in any such as bistable rotaxanes, represent a piece of really way to be a celebrity, and it sort of happens to you disruptive chemistry. In terms of molecular electronic overnight, and also to your family. devices that are based on bistable rotaxanes, it turns out that when a congregation of these molecules is PNAS: What motivates your research? introduced into what’s called a crossbar device be- ’ tween two terminals, hundreds or thousands of mole- Stoddart: I happen to be a farmer s boy. So, when cules can be trapped as a monolayer between the people ask me, I say you need the strength of a horse crossing point between two wires. The bistable rotax- and the hide of an elephant, particularly in the early days when you’re doing something that’s creative. anes can be made to switch between on and off states. People are not very accepting of new things; you’ve This control gave us the basis for creating, ultimately, got to be able to take the hits and the barbs that come a 160-kilobit random access memory. Now we are your way. In addition to the strength of a horse and the mounting these molecular switches into metal–organic hide of an elephant, you need the work ethic of a frameworks in search of more robust settings. honey bee. I’m basically on 16 hours a day, seven days a week. PNAS: In 2014 you were inducted into the National Academy of Sciences. Your Inaugural Article focused PNAS: What do you see as the future of molecular on molecular switches, which can be shifted between nanotechnology? two or more stable states (4). Again, bistable rotax- anes played a major role and enabled the alteration Stoddart: I happen to be reading a book by Bill of electric states in the switches. What makes bistable Bryson at the moment that zeros in on flight in the year rotaxanes a useful design component of molecular 1927, about 20 years after the Wright brothers. Flight switches and other molecular technology? was a precarious pursuit in the beginning. There was still not much certainty about getting a contraption Stoddart: We put our faith in the fact that we had into the air without it bursting into flames or only invented a new bond, which opens up all kinds of going a few yards and dropping into a forest beyond a different movements of component parts with respect make-shift runway. And yet, yesterday I flew back from to each other within molecules. We can move com- Frankfurt in a dream-liner, the biggest airplane I’ve ponents by a nanometer or two, or several nanome- ever been in. That’s the kind of extrapolation that I ters, very easily using this type of bonding, whereas think one needs to make in terms of molecular motors previously chemists were limited to torsions about and machines. How fast will the transformation occur, single or double bonds. Azobenzene is the famous I’m not sure, but I have no doubt it has been given an example where it is possible to attain circular motion, impetus by the decision the committee made in Stock- albeit limited. I think the mechanical bond opens up holm this year. We’re only scratching the surface pres- an endless amount of scope for scientists to explore ently. I’m hopeful the prize will give a huge fillip to switching and other mechanical properties. It has to the field.

1 Feynman R (1959) Plenty of room at the bottom. American Physical Society. Available at www.pa.msu.edu/∼yang/RFeynman_plentySpace.pdf. Accessed November 11, 2016. 2 Barin G, Forgan RS, Fraser Stoddart J (2012) Mechanostereochemistry and the mechanical bond. Proc R Soc A 468(2146):2849–2880. 3 Anelli PL, Spencer N, Fraser Stoddart J (1991) A molecular shuttle. J Am Chem Soc 113(13):5131–5133. 4 McGonigal PR, et al. (2015) Electrochemically addressable trisradical rotaxanes organized within a metal-organic framework. Proc Natl Acad Sci USA 112(36):11161–11168.

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